High-dose-rate brachytherapy (HDR-BT) is a technique for treating cancerous tumors in which needles are inserted inside or close to the tumor. A radiation source travels inside each needle, depositing a radiation dose pattern inside the tumor over one or more treatment sessions, with the goal of killing all of the tumor cells and sparing radiation-sensitive normal tissue as much as possible. Brachytherapy enables the delivery of higher radiation doses than would be possible with external beam radiation therapy (EBRT), wherein radiation beams from outside the patient must pass through healthy tissues on the way to tumors. With brachytherapy, the radiation dose that can be delivered to tumors is still limited by the presence of adjacent healthy tissues. When treating cervical cancer, tumor dose limiting tissues are the rectum, bladder, and sigmoid colon. For breast cancer lumpectomy cavities treated with brachytherapy, the deliverable dose is limited by the skin on the surface of the breast, the ribs, and normal breast tissue. For prostate cancer, the urethra, rectum, and bladder limit tumor dose.
A major limitation of conventional brachytherapy is that the radiation dose distribution delivered with brachytherapy sources is radially symmetric about the source axis, which limits the tumor dose conformity achievable. Further, in the radiation oncology field, increased radiation doses delivered in fewer treatment fractions, or hypofractionation, is becoming increasingly important both for improving patient care and reducing treatment cost.
Conventional HDR-BT delivers radially-symmetric dose distributions in cervical cancer patients, which limits the radiation dose that can be delivered to tumor without exceeding the tolerance doses of the organs-at-risk (OARs) adjacent to or inside the tumor, especially in cases where the tumor is bulky (>40 cc), laterally-extended, or non-symmetric, thus comprising treatment effectiveness.
The use of interstitial brachytherapy is an option to overcome this drawback and is recommended by the American Brachytherapy Society (ABS). Large tumor can be conformally treated with needles. Another option recently introduced, is the use of supplementary needles along with intracavitary applicator (IS+ICBT), tandem and ring or tandem and ovoids plus needles have been introduced. These applicators enable the enhanced tumor coverage under magnetic resonance image (MRI)-guidance, yet, at the cost of more invasive treatment due to the presence of interstitial needles. In addition, even if the number of catheters, locations of catheters, and the source dwell times are computed in an optimized fashion, the resulting dose distributions may still be subject to the constraint that the source emits radially-symmetric dose distributions.
The rotating shield brachytherapy (RSBT) and dynamic modulated brachytherapy (DMBT) approaches have been introduced as a means to improve intracavitary brachytherapy dose distributions for rectal and cervical cancer. Dynamic-shield RSBT (D-RSBT) allows the use of different azimuthal emission angles during the delivery via a layered shielding apparatus with each layer independently rotatable to form different emission windows. The major drawback of D-RSBT lies on the limit of its maximal azimuthal emission angle that can be formed by the apparatus. With delivery times of 20-30 min per treatment fraction, D-RSBT can produce better delivery plans than S-RSBT, while S-RSBT may perform better when the delivery time is limited (e.g. <20 min/fx). Therefore, there is a need for a noninvasive, conformal brachytherapy treatment that can combine the power of S-RSBT and D-RSBT, thus performing better than both S-RSBT and D-RSBT in the sense of balancing the treatment time and dose quality.
In addition, certain forms of cancer need specialized application. For example, prostate cancer is the most common non-skin cancer in men, with 238,590 new diagnoses in 2013, a 9.5% increase over the 2010 estimate. Most prostate cancer patients have localized prostate cancer and a variety of treatment options including surgery, external beam radiotherapy (EBRT), low-dose-rate brachytherapy (LDR-BT), HDR-BT, and combinations thereof. Prostate cancer treatment cost is at least $19,901 per patient, and currently 82% of men diagnosed with prostate cancer receive surgery, brachytherapy or EBRT. If healthcare trends develop such that all low-risk prostate cancer patients (47.6% of patients) receive active surveillance and 30% of those patients receive treatment within 5 years of diagnosis, there will still be nearly 134,000 men who were diagnosed with prostate cancer in 2013 and who will receive treatment within the next five years.
Although long-term (10+ year) biochemical disease-free survival is high and tends to increase with radiation dose delivered, 29,720 men still died of prostate cancer in 2013. While achieving tumor control is paramount, prostate cancer patients may live with the side effects of their treatment for decades, and anticipated side effects play a strong role in treatment decisions. Treatment decisions are often based on anticipated side effects, such as urinary incontinence, urethral stricture, rectal bleeding, and sexual dysfunction. Existing treatments all have reducible incidences of side effects that can impact patients' quality of life for decades.
Existing brachytherapy techniques offer advantages over other treatments in both survival and side effects with the exception of increased urinary complications, highlighting a critical need for a lower-toxicity treatment technique. In a large-scale literature review (848 of 18,000 published abstracts), Grimm et al (2012) found that in low-risk patients brachytherapy provides superior long-term (10+ year) biochemical relapse-free survival to EBRT and surgery, in intermediate-risk patients brachytherapy alone is equivalent to EBRT in combination with brachytherapy and superior to surgery and EBRT alone, and in high-risk patients EBRT in combination with brachytherapy is superior to more localized treatments such as surgery alone, brachytherapy alone, or EBRT alone. The benefits of brachytherapy in obtaining long-term relapse-free survival are suspected to be due to the dose escalation achievable that would not be possible with EBRT alone. Surgery, even using the Da Vinci robot (Intuitive Surgical, Inc., Sunnyvale, Calif.), has been reported to have greater risks of urinary incontinence and sexual dysfunction than radiotherapy techniques, in that brachytherapy has a 3-fold higher rate of return than surgery to baseline urinary function at 36 months, and a 5-fold higher rate of return to baseline sexual function. HDR-BT and combined EBRT and HDR-BT have equivalent or lower sexual dysfunction and gastro-intestinal toxicity than EBRT alone, but greater late grade ≥3 urethral stricture rates at 5 years of 7-10% versus 1-2% for EBRT alone.
Therefore, there is thus a critical need in the urology and radiation oncology fields for prostate cancer treatment techniques with an equal or greater cancer control probability than current techniques, but with reduced toxicity.